High prevalence of TSC2 mutations in lung tissue samples from patients with sporadic lymphangioleiomyomatosis

Extract Lymphangioleiomyomatosis (LAM) is a rare and progressive cystic lung disease occurring predominantly in premenopausal woman, with rare cases reported in men. The pathogenesis is thought to be due to proliferative smooth muscle-like cells (LAM cells) that cause lung cystogenesis. LAM occurs both sporadically (sporadic-LAM), accounting for the majority of clinically diagnosed individuals, and in association with Tuberous Sclerosis Complex (TSC-LAM) [1]. Bi-allelic mutation in TSC2 activates mTOR complex 1 (mTORC1), which promotes unchecked cellular proliferation and growth [2]. Pharmacological inhibition of mTORC1 with rapamycin, an allosteric mTORC1 inhibitor, has been shown to stabilise lung function and attenuate disease progression in most patients with LAM [3].